DESCRIPTION, OVERALL (provided by applicant): Our research involves specific aims distributed among three projects served by three cores. Of these, some are currently in progress as a result of new findings discovered during the present grant period. The remainder represent new projects. Almost all of the protocols depend upon collaborative relationships between at least 2 projects, and draw upon at least one core. Project by Coe uses human subjects in highly focused clinical research center (CRC) protocols aimed at understanding the pathophysiology of plaque, CD plugging and stone formation in terms of hormonal and mineral dynamics related to feeding. Project by Lingeman plans continued mapping and biopsy of the many SF phenotypes we have not yet studies. Project by Evan plans continued histopathologic and mineral analysis of SF biopsies. We plan a critical experiment to determine whether the initial plaque site is the ascending or the descending limb of the THL. We will continue to produce analyses of SF patient groups in terms of treatment outcomes and phenotype characterization.